Leucine Crystals in the Urine – Still enigmatic after more than 150 years

Exemplary case

A 65-year-old patient with a history of cholangiocarcinoma was admitted with abdominal pain, increasing ascites and jaundice. He was diagnosed with spontaneous bacterial peritonitis. Shortly afterwards he developed septic shock and an acute kidney injury. The urinary sediment showed a lot of yellow-colored tubular epithelial cells, some granular casts, as well as multiple yellow-brown globes, identified as leucine crystals.

Discussion

Leucine crystals present themselves “in the shape of more or less yellow-tinged, highly refracting spheres […]; and by suitable illumination many of them will be found marked with radiating and concentric striae. The spherules further exhibit a peculiar disposition to aggregate, appearing partially to merge where two edges come together.”

Leucine crystals and their presence in the urine were first described by Frerichs and Staedeler around 1854 in a series of papers establishing the presence of leucine and tyrosine in the liver and other tissues. It was soon established that leucine crystals in urine were mostly found “in rapidly destructive diseases of the liver, [such] as acute yellow atrophy or phosphorus poisoning, but occasionally also in typhus and smallpox.”

More or less 170 years after their first description, the true meaning of leucine crystals in the urinary sediment is still unclear. Personally, we have only seen them in patients with acute cholestatic liver diseases. It is probably safe to assume that they demonstrate the presence of high amounts of leucine in the urine and that this is not due to a renal reabsorption defect. Since leucine excretion in stable patients with liver cirrhosis is not increased ⁵, there must be some specific – probably acute – liver pathology that results in high levels of leucine appearing in the urine. Unfortunately, there have been no systematic analyses of these questions.

As of today, we can only reiterate this quote from more than a century ago: “The appearance of leucin and tyrosin [crystals] in the urine is unquestionably indicative of a very marked interruption in the metabolic processes of the body, and especially of the liver, and is evidence of the great severity of the primary disease.”